Vuchetich J P, Dunnette J, Lunetta K L, Weinshilboum R M, Price R A
Department of Psychology, School of Arts and Sciences, University of Pennsylvania, Philadelphia.
Genet Epidemiol. 1991;8(4):237-51. doi: 10.1002/gepi.1370080405.
Although the structural gene for human dopamine-beta-hydroxylase (DBH) has been cloned, the mechanism by which DBH physical properties and activity are regulated is not well understood. Previous reports have suggested that three-allele or two-locus models may account for the genetic regulation of these traits in human blood. It is an interesting challenge to determine the extent to which quantitative analyses will complement or guide molecular genetic studies. In this study we analyzed data on the physical property of DBH thermal stability and DBH activity in 230 individuals in 53 families in an attempt to clarify genetic mechanisms for the inheritance of these traits. Commingling and segregation analyses of the thermal stability data provided the first clear evidence of a major gene polymorphism for DBH thermal stability analyzed as a quantitative trait. Major gene transmission was supported within a mixed model (chi 2[3] = 13.39, P less than .004). In keeping with earlier findings, similar analyses of DBH activity provided strong evidence of genetic transmission. However, in our data support for a major gene polymorphism was equivocal (chi 2(2) = 2.99, P = .22).
尽管人类多巴胺-β-羟化酶（DBH）的结构基因已被克隆，但DBH物理性质和活性的调节机制仍未完全明确。此前的报道表明，三等位基因或双基因座模型可能解释人类血液中这些性状的遗传调控。确定定量分析在多大程度上能够补充或指导分子遗传学研究是一项有趣的挑战。在本研究中，我们分析了53个家庭中230名个体的DBH热稳定性物理性质和DBH活性数据，试图阐明这些性状遗传的遗传机制。对热稳定性数据的混合和分离分析首次明确证明了将DBH热稳定性作为数量性状分析时存在一个主要基因多态性。在一个混合模型中支持主要基因传递（χ2[3]=13.39，P<0.004）。与早期研究结果一致，对DBH活性的类似分析提供了遗传传递的有力证据。然而，在我们的数据中，对主要基因多态性的支持并不明确（χ2(2)=2.99，P=0.22）。
